Discovery and evaluation of Cav3.1-selective T-type calcium channel blockers. Issue 23 (1st December 2017)

• Record Type: Journal Article
• Authors: Bezençon, Olivier; Remeň, Luboš; Richard, Sylvia; Roch, Catherine; Kessler, Melanie; Moon, Richard; Mawet, Jacques; Ertel, Eric A.; Pfeifer, Thomas; Capeleto, Bruno
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 23(2017)
• Page Start: 5322
• Page End: 5325
• Publication Date: 2017-12-01
• Subjects: AcOH acetic acid -- 9-BBN 9-borabicyclo(3.3.1)nonane -- DAST diethylaminosulfur trifluoride -- DIPEA N, N-diisopropylethylamine -- DMAP 4-(dimethylamino)pyridine -- DMF N, N-dimethylformamide -- EDC·HCl 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride -- HOBt hydroxybenzotriazole -- NBS N-bromosuccinimide -- tBu tert-butyl -- Tf trifluorosulfonyl -- THF tetrahydrofuran; T-type calcium channel -- Selective Cav3.1-blockers -- Pyrazoles; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.09.063
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: We identified and characterized a series of pyrazole amides as potent, selective Cav 3.1-blockers. This series culminated with the identification of pyrazole amides5a and12d, with excellent potencies and/or selectivities toward the Cav 3.2- and Cav 3.3-channels. This compound displays poor DMPK properties, making its use difficult for in vivo applications. Nevertheless, this compound as well as analogous ones are well-suited for in vitro studies.